Many diseases (e.g., cancer, inborn errors of metabolism) can be thought of as diseases of normal development. Understanding the nature of these diseases will therefore require an understanding of normal development. The cellular slime mold Dictyostelium discoideum is an excellent model system for studying development. A great deal of evidence has accumulated over the past several years which indicates that different genes are expressed at different stages of slime mold development. The purpose of this proposal is to take a developmentally regulated system which has been well defined in terms of enzymology, protein chemistry, genetics and experimental embryology and develop a sound foundation for its eventual understanding in molecular terms. The system to be studied is the regulation of UDP-glucose pyrophosphorylase production and of other polypeptides which show evidence of being regulated in a coordinate fashion with this protein. I propose to partially purify the mRNAs coding for these polypeptides, synthesize and identify the homologous cDNA clones, and use the purified DNAs as probes to measure rates of synthesis, turnover and accumulation of the specific mRNAs. I also propose to do an initial screening of mutants which have been shown to be defective in the production of enzyme activity and to isolate additonal mutants for eventual mapping and further characterization. Experiments in this proposal will also result in an evaluation of the potential use of poly(U)-Sepharose as a purification step in the isolation of developmentally regulated mRNAs.